Efficacy and Safety of Niraparib as Maintenance Treatment in Patients With Extensive-Stage SCLC After First-Line Chemotherapy: A Randomized,Double-Blind,Phase 3 Study

IntroductionZL-2306-005 is a randomized, double-blind, multicenter phase 3 study evaluating the efficacy and safety of niraparib, a poly(adenosine diphosphate-ribose) polymerase inhibitor, as first-line maintenance therapy in Chinese patients with platinum-responsive, extensive-stage SCLC (ES-SCLC).MethodsPatients with complete response (CR) or partial response (PR) to standardized, platinum-based first-line chemotherapy were randomized 2:1 to receive niraparib or placebo (300 mg [baseline body weight ≥ 77 kg, platelet count ≥ 150,000/μL] or 200 mg) once daily until progression or unacceptable toxicity. Primary end points were progression-free survival (PFS) (blinded independent central review) and overall survival (sample size planned: 591 patients). Secondary end points included investigator-evaluated PFS and safety.ResultsZL-2306-005 was terminated early owing to ES-SCLC treatment landscape changes (data cutoff: March 20, 2020). During July 2018–February 2020, a total of 185 of 272 patients screened were randomized (niraparib: n = 125 [CR = 1, PR = 124]; placebo: n = 60 [CR = 1, PR = 59]). Median (95% confidence interval [CI]) PFS (blinded independent central review) was 1.54 months (1.41–2.69, niraparib) and 1.36 months (1.31–1.48, placebo); hazard ratio (HR) = 0.66 (95% CI: 0.46–0.95, p = 0.0242). Median overall survival was 9.92 months (9.33–13.54, niraparib) and 11.43 months (9.53–not estimable, placebo); HR = 1.03 (95% CI: 0.62–1.73, p = 0.9052). Median investigator-evaluated PFS was 1.48 months (1.41–2.56, niraparib) and 1.41 months (1.31–2.00, placebo); HR = 0.88 (95% CI: 0.61–1.26; p = 0.4653). Grade greater than or equal to 3 adverse events occurred in 34.4% (niraparib) and 25.0% (placebo) of patients.ConclusionsZL-2306-005 did not reach primary end points. Nevertheless, niraparib as maintenance therapy modestly improved PFS in patients with platinum-responsive ES-SCLC, with acceptable tolerability profile and no new safety signal.     

维生素K_2对MDS细胞株SKM-1增殖抑制和诱导凋亡作用的研究

目的研究维生素K2（VK2）对骨髓增生异常综合征（MDS）细胞株SKM-1的增殖抑制和诱导凋亡作用并探讨其可能机制。方法 （1）应用四甲基偶氮唑蓝（MTT）比色法测定VK2对SKM-1细胞增殖的抑制作用;（2）通过Annexin-V/PI标记VK2作用后的SKM-1细胞,用流式细胞术分析其凋亡情况;（3）通过流式细胞术检测SKM-1细胞线粒体膜电位（ΔΨm）的变化;（4）应用RT-PCR检测凋亡抑制基因Survivin的表达,分析VK2诱导SKM-1细胞凋亡的机制。结果 （1）5、10、20、40μmol/L VK2分别作用于SKM-1细胞24、48、72 h后,细胞增殖抑制明显（均P〈0.05）,生长抑制率的增加呈剂量依赖性（P〈0.05）;（2）不同浓度VK2处理后48h,SKM-1细胞发生凋亡（均P〈0.01）,细胞凋亡率的增加呈剂量依赖性（P〈0.05）;（3）不同浓度VK2作用后24 h,SKM-1细胞线粒体膜电位降低明显（均P〈0.01）,且呈剂量依赖性（P〈0.01）;（4）不同浓度VK2处理后48 h,SKM-1细胞Survivin基因表达随着VK2浓度的增大而明显下调（均P〈0.05）。结论 （1）VK2对SKM-1细胞增殖有抑制作用,呈剂量依赖性;（2）VK2可诱导SKM-1细胞早期凋亡,呈剂量依赖性;（3）在此凋亡过程中,SKM-1细胞线粒体膜电位降低、凋亡抑制基因Survivin表达下调;（4）Survivin基因的表达下调可能是VK2诱导SKM-1细胞凋亡的机制之一。     

Association of MicroRNA-196a-2 Gene Polymorphism with Gastric Cancer Risk in a Chinese Population

Background  

It has been proposed that single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) could affect the expression of the miRNA and contribute to the susceptibility of human tumors. However, the role of genetic variant (T/C) in miR-196a-2 in gastric cancer susceptibility is still unknown.     

扩大分离腰肌前间隙在后腹腔镜肾根治性切除术中的应用

目的优化后腹腔镜肾根治性切除术的手术方法及临床效果。 方法回顾性分析2013年9月至2016年9月我院143例后腹腔镜肾根治性切除术的肾肿瘤患者临床资料,其中65例按常规手术步骤完成手术（对照组）;78例行扩大分离腰肌前间隙（研究组）,判定标准为分离范围：上界至膈肌穹隆顶,下界至肾周筋膜锥尖部,内侧至切开肾蒂腹侧表面肾筋膜,显露疏松网状组织。比较两组手术时间、出血量、围手术期并发症及术后住院时间等。 结果两组患者性别比例、年龄、肿瘤大小、TNM分期等资料差异无统计学意义。对照组和研究组手术时间分别为（95.1±15.1）min和（53.6±20.3）min,术中出血量分别为（80.6±25.6）ml和（45.1±19.7）ml,两组比较差异均存在统计学意义（P<0.05）;术中并发症发生率分别为6.2%（4/65）和1.3%（1/78）,术后肠功能恢复时间（2.1±0.4）d和（2.0±0.4）d,术后住院时间（6.2±1.8）d和（5.7±1.5）d,两组比较差异均无统计学意义（P>0.05）。对照组4例并发症全部为术前未知存在异位动脉,结扎肾血管后创面持续渗血,其中1例迅速分离出异位动脉后切断完成手术,其余3例中转开放手术。研究组1例并发症为气胸,术后胸腔闭式引流3 d后治愈。 结论后腹腔镜肾根治性切除术中扩大分离腰肌前间隙,是对常规手术方法的优化,可缩短手术时间,减少围手术期并发症。     

Postoperative morbidity and mortality after anterior resection with preventive diverting loop ileostomy versus loop colostomy for rectal cancer: A updated systematic review and meta-analysis

The purpose of this meta-analysis was to evaluate the perioperative morbidity after anterior resection with diverting loop ileostomy (LI) versus colostomy (LC) and its reversal for rectal cancer. The studies on the application of loop ileostomy versus loop colostomy in anterior resection published from January 2000 to January 2020 were searched in the databases of Pubmed, Embase, Cochrane library, and Clinical trials. All randomized controlled trials (RCTs) and cohort studies were included according to inclusion criteria. Eight studies (2 RCTs and 6 cohort studies) totaling 1451 patients (821 LI and 630 LC) were included in the meta-analysis. The morbidity related to stoma formation and closure did not demonstrate significant differences. Significantly more LCs were complicated by stoma prolapse & retraction (OR:0.26,95%CI:0.11–0.60,P = 0.001), parastomal hernia (OR = 0.52,95%CI:0.30–0.88, P = 0.01), surgical site infection (SSI) (OR = 0.24,95%CI:0.11–0.49,P < 0.0001) and incisional hernias (OR = 0.39,95%CI:0.19–0.83,P = 0.01) than by LIs. Patients with LI demonstrated significantly more complications related to the stoma, such as dehydration (OR = 0.52,95%CI:0.30–0.88, P = 0.01) and ileus (OR = 2.23,95%CI:1.12–4.43, P = 0.02) than patients with LC. While after the subgroup analysis of different publication years, LI could reduce the risk of the morbidity after stoma formation in previous years group (P = 0.04) with a lower heterogeneity (I² = 37%); LC could reduce the incidence of parastomal dermatitis in recent years group (P < 0.0001) without heterogeneity in each subgroup (I² = 0%). Cumulative meta-analysis detected significant turning points in dehydration, SSI, and ileus. This meta-analysis recommends diverting LI in the anterior resection for rectal cancer, but there is a risk of dehydration, irritant dermatitis, and ileus.     

Fas／FasL、Bax及Bcl-2在1型糖尿病大鼠中的表达及其与凋亡的关系

目的探讨Fas／FasL、Bax及Bcl-2在1型糖尿病大鼠中的表达及其与凋亡的关系。方法链脲佐菌素诱导1型糖尿病大鼠模型,TUNEL法检测1型糖尿病大鼠（模型组）及其正常大鼠（正常组）胰腺组织的细胞凋亡,应用RT-PCR法及其免疫组化法检测Fas／FasLmRNA、Bcl-2／BaxmRNA及蛋白的表达情况。结果模型组胰腺组织中细胞的凋亡比正常组的大鼠多,Fas／FasLmRNA及BaxmRNA的表达水平在模型组的表达均比正常组显著提高,而Bcl-2mRNA的表达水平显著下降,两者相比差异均有统计学意义（均P〈0．05）。随血糖的升高,凋亡指数亦增加,Fas／FasLmRNA及BaxmRNA的表达升高,但Bcl-2mRNA的表达下降。结论Fas／FasL的表达及其细胞凋亡在大鼠l型糖尿病的形成中起着重要作用,Bax对凋亡起促进作用,Bcl-2对凋亡起抑制作用。     

P120连环素在乳腺浸润性导管癌中的表达与临床病理意义

目的：探讨P120在乳腺浸润性导管癌中的表达及其与临床病理特征的关系。方法：采用免疫组化方法检测84例乳腺浸润性导管癌组织中ER、PR、c-erbB-2及P120的表达情况;84例乳腺癌病例中有43例同时取相应新鲜肿瘤组织和癌旁的正常组织,采用RT-PCR方法检测其P120的表达情况。结果：84例乳腺浸润性导管癌中P120蛋白在细胞膜正常表达率为39.3%。43例乳腺癌术中留取的新鲜肿瘤组织中P120 mRNA阳性表达率为37.2%。P120在乳腺浸润性导管癌与癌旁正常组织中的表达差异有统计学意义（P〈0.01）。P120表达与淋巴结转移、临床分期及c-erbB-2表达均有明显相关性（P〈0.05）,P120蛋白表达与患者年龄、肿瘤大小、肿瘤组织学分级及ER、PR表达间均未见明显相关性（P〉0.05）。结论：P120的异常表达可能反映了乳腺浸润性导管癌的侵袭性生物学行为。     

Association between plasma homocysteine levels and obstructive sleep apnoea in patients with ischaemic stroke

We aimed to investigate the association between plasma homocysteine and obstructive sleep apnoea (OSA) syndrome in patients with ischaemic stroke. A total of 102 patients with ischaemic stroke were classified into four OSA groups based on their apnoea–hypopnoea index (AHI): absent (AHI < 5/hour); mild (5–14/hour); moderate (15–30/hour); and severe (>30/hour). The mean (±standard deviation) homocysteine levels in the four OSA groups were: absent, 8.98 ± 3.74 μmol/L; mild, 11.46 ± 3.31 μmol/L; moderate, 14.18 ± 4.36 μmol/L; and severe, 18.57 ± 4.56 μmol/L; and these differences were statistically significant (p < 0.001). The Pearson correlation analysis revealed a positive correlation between homocysteine levels and the severity of AHI (r = 0.482, p < 0.001). Multiple linear regression analysis showed that AHI and folate were independent predictors of homocysteine levels (R² = 0.539, p < 0.001, β for AHI = 0.259, β for folate = –0.400). In conclusion, the severity of OSA is significantly associated with elevated homocysteine levels in patients with ischaemic stroke, and this association is independent of other factors that cause elevation in homocysteine.     

An evaluation of the PowerSeq™ Auto System: A multiplex short tandem repeat marker kit compatible with massively parallel sequencing

Capillary electrophoresis (CE) and multiplex amplification with fluorescent tagging have been routinely used for STR typing in forensic genetics. However, CE-based methods restrict the number of markers that can be multiplexed simultaneously and cannot detect any intra-repeat variations within STRs. Several studies already have indicated that massively parallel sequencing (MPS) may be another potential technology for STR typing. In this study, the prototype PowerSeq™ Auto System (Promega) containing the 23 STR loci and amelogenin was evaluated using Illumina MiSeq. Results showed that single source complete profiles could be obtained using as little as 62 pg of input DNA. The reproducibility study showed that the profiles generated were consistent among multiple typing experiments for a given individual. The mixture study indicated that partial STR profiles of the minor contributor could be detected up to 19:1 mixture. The mock forensic casework study showed that full or partial profiles could be obtained from different types of single source and mixture samples. These studies indicate that the PowerSeq Auto System and the Illumina MiSeq can generate concordant results with current CE-based methods. In addition, MPS-based systems can facilitate mixture deconvolution with the detection of intra-repeat variations within length-based STR alleles.